Endogenous fungal endophthalmitis is a potentially blinding complication of disseminated fungal infection or accidental intravenous inoculation. The incidence of endophthalmitis appears to relate to factors which enhance disseminated infection by opportunistic fungi: neoplastic disease, immunosuppressive therapy, and concurrent antibiotic therapy. The most common causes of endogenous fungal endophthalmitis in man are Candida albicans and Aspergillus fumigatus. This project will study the pathogenesis, diagnosis, and therapy of endogenous Candida and Aspergillus endophthalmitis in the rabbit and sub-human primate (Macaca mulatta). Our preliminary investigations have demonstrated that progressive C. albicans endophthalmitis can be produced by intravenous injection of blastospores in rabbits and rhesus monkeys and that the early retinochoroidal stage in the rabbit can be modified by antifungal therapy and corticosteroids. The significance of strain and species of fungus; phase of the organism; inoculum size; and method of introduction in regard to incidence and severity of ocular disease will be defined in these models. Newer methods for detection of of fungal antibody and antigen in ocular fluids will be appraised. The effects of glucocorticosteroid therapy on the development and progression of Candida and Aspergillus endophthalmitis will be determined. The safety of intravitreal antifungal antibiotics in the primate eye will be assessed by light, scanning, and transmission microscopy; electroretinography; and autoradiography. The project will evaluate the efficacy of various antifungal agents on established fungal endophthalmitis in the rabbit by quantitative ocular cultures. The validity of these observations will be assessed in the subhuman primate model. The results of the studies should amplify our understanding of the pathogenesis of ocular fungi and have direct application to the diagnosis and therapy of various forms of fungal endophthalmitis.